PMID- 31049785 OWN - NLM STAT- MEDLINE DCOM- 20191210 LR - 20200225 IS - 1559-1166 (Electronic) IS - 0895-8696 (Linking) VI - 68 IP - 4 DP - 2019 Aug TI - Myeloid-Related Protein 8/14 Participates in the Progression of Experimental Pneumococcal Meningitis by Augmentation of Inflammation. PG - 631-639 LID - 10.1007/s12031-019-01314-y [doi] AB - It has been reported that myeloid-related protein 8/14 (MRP8/14) participates in the progression of inflammation after release from neutrophils and monocytes. This study aimed to clarify the mechanism(s) of the MRP8/14-augmented inflammatory response in mice with pneumococcal meningitis. Streptococcus pneumoniae (SP) meningitis was established by intracerebral injection of SP suspension. Balb/c mice were randomly divided into four groups and received the following injections: phosphate-buffer saline (PBS), MRP8/14 alone, SP alone, and SP plus MRP8/14. At 6 h, 24 h and 48 h postinfection, the clinical disease status was measured by the modified neurological severity score test, body weight loss and degree of cerebral edema; mice were anaesthetized, blood samples and brain samples were collected and brain inflammation was detected by haematoxylin and eosin (HE) staining; tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), C-reactive protein (CRP) and monocyte chemoattractant protein-1 (MCP-1) levels in serum and brain homogenates were assessed by an enzyme-linked immunosorbent assay (ELISA), and the mRNA levels of the above cytokines in brain homogenates were measured by polymerase chain reaction (PCR); and the expression of nuclear factor-kappa B (NF-kappaB) p65 in brain tissues was determined by immunohistochemical assay. In this study, we identified that MRP8/14 substantially augmented the SP-stimulated inflammatory response, aggravated clinical disease status and exacerbated SP-induced brain edema in a murine model of pneumococcal meningitis. Exogenous administration of MRP8/14 significantly enhanced mRNA and protein expression of the proinflammatory cytokines and chemokines TNF-alpha, CRP, IL-6 and MCP-1 in brain homogenates and serum from mice with pneumococcal meningitis, which may be related to the NF-kappaB signalling pathway. We further found that MRP8/14 strongly augmented SP-induced phosphorylation of NF-kappaB p65 in brain tissue slices from the same model. In conclusion, our results indicated that MRP8/14 augmented the inflammatory response in mice with pneumococcal meningitis and contributed to the development of disease, which was probably through NF-kappaB signalling pathway activation. FAU - Huang, Danping AU - Huang D AD - Department of Neurology, Children's Hospital of Soochow University, Suzhou, 215000, Jiangsu, People's Republic of China. FAU - Liu, Min AU - Liu M AD - Department of Neurology, Children's Hospital of Soochow University, Suzhou, 215000, Jiangsu, People's Republic of China. FAU - Zhou, Yang AU - Zhou Y AD - Pediatric Department, Suzhou kowloon Hospital Shanghai Jiao Tong University, Suzhou, 215000, Jiangsu, People's Republic of China. FAU - Zhao, Bingxin AU - Zhao B AD - Department of Neurology, Children's Hospital of Soochow University, Suzhou, 215000, Jiangsu, People's Republic of China. FAU - Chen, Xuqin AU - Chen X AD - Department of Neurology, Children's Hospital of Soochow University, Suzhou, 215000, Jiangsu, People's Republic of China. xuqinlili@163.com. LA - eng GR - BK20161227/Natural Science Foundation of Jiangsu Province/ GR - LGY2017091/Six One Projects of Jiangsu Province/ GR - BE2018661/Jiangsu Province Program of Key research and development plan/ GR - LCZX201810/Suzhou Clinical Key Disease Diagnosis and Treatment Technology Special Project/ PT - Journal Article DEP - 20190502 PL - United States TA - J Mol Neurosci JT - Journal of molecular neuroscience : MN JID - 9002991 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Interleukin-6) RN - 0 (Leukocyte L1 Antigen Complex) RN - 0 (Transcription Factor RelA) RN - 0 (Tumor Necrosis Factor-alpha) RN - 9007-41-4 (C-Reactive Protein) SB - IM MH - Animals MH - Anti-Inflammatory Agents/*pharmacology/therapeutic use MH - Brain/drug effects/metabolism MH - C-Reactive Protein/genetics/metabolism MH - Chemokine CCL2/genetics/metabolism MH - Interleukin-6/genetics/metabolism MH - Leukocyte L1 Antigen Complex/*pharmacology/therapeutic use MH - Male MH - Meningitis, Pneumococcal/drug therapy/*metabolism MH - Mice MH - Mice, Inbred BALB C MH - Transcription Factor RelA/genetics/metabolism MH - Tumor Necrosis Factor-alpha/genetics/metabolism OTO - NOTNLM OT - CRP OT - IL-6 OT - MCP-1 OT - MRP8/14 OT - NF-kappaB OT - Pneumococcal meningitis OT - TNF-alpha EDAT- 2019/05/03 06:00 MHDA- 2019/12/18 06:00 CRDT- 2019/05/04 06:00 PHST- 2018/10/24 00:00 [received] PHST- 2019/03/25 00:00 [accepted] PHST- 2019/05/03 06:00 [pubmed] PHST- 2019/12/18 06:00 [medline] PHST- 2019/05/04 06:00 [entrez] AID - 10.1007/s12031-019-01314-y [pii] AID - 10.1007/s12031-019-01314-y [doi] PST - ppublish SO - J Mol Neurosci. 2019 Aug;68(4):631-639. doi: 10.1007/s12031-019-01314-y. Epub 2019 May 2.